Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor.
Resistance to oxidative stress by chronic infusion of angiotensin II in mouse kidney is not mediated by the AT2 receptor.
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小鼠肾脏长期输注血管紧张素 II 对氧化应激的抵抗力不是由 AT2 受体介导的。
DOI：
10.1152/ajprenal.00322.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
B. Braam
中科院分区：
文献类型：
--
作者：
S. Wesseling;D. Ishola;J. Joles;H. Bluyssen;H. Koomans;B. Braam
野生型小鼠对血管紧张素II（ANG II）诱导的肾损伤具有抵抗力，因此成为研究肾脏对ANG II防御机制的理想模型。本研究旨在测试ANG II是否通过肾皮质中的血管紧张素II的2型受体（AT2受体）诱导抗氧化基因的表达，从而抵消促氧化作用。将ANG II注入雌性C57BL/6J小鼠体内28天，其中一个亚组在最后3天接受AT2受体拮抗剂（PD - 123,319）。ANG II诱发了高血压和主动脉肥厚，但未出现蛋白尿和肾损伤。尿一氧化氮代谢产物（NOx）减少，脂质过氧化物（TBARS）排泄量保持不变。肾皮质中NADPH氧化酶成分的表达降低，但在主动脉中升高。血红素加氧酶 - 1（HO - 1）在肾皮质和主动脉中均被诱导。相比之下，ANG II可能增加了肾脏中AT2受体的表达，但在主动脉中没有。AT2受体阻断加剧了ANG II灌注小鼠的高血压，逆转了ANG II对NOx排泄的影响，但不影响TBARS。尽管具有升压作用，但短期AT2受体阻断后肾皮质中促氧化基因的表达降低而非升高，并且ANG II诱导的肾HO - 1表达恢复正常。因此，在小鼠中长期注入ANG II会诱发高血压，但不会诱发氧化应激。与主动脉中的反应不同，肾皮质中NADPH氧化酶成分的基因表达没有增强。尽管给予ANG II诱导了肾皮质AT2受体的表达，但阻断该受体并未揭示AT2受体是肾内促氧化作用的抑制因子。
Wild-type mice are resistant to ANG II-induced renal injury and hence form an attractive model to study renal defense against ANG II. The present study tested whether ANG II induces expression of antioxidative genes via the AT2 receptor in renal cortex and thereby counteracts prooxidative forces. ANG II was infused in female C57BL/6J mice for 28 days and a subgroup received AT2 receptor antagonist (PD-123,319) for the last 3 days. ANG II induced hypertension and aortic hypertrophy; proteinuria and renal injury were absent. Urinary nitric oxide metabolites (NOx) were decreased, and lipid peroxide (TBARS) excretion remained unchanged. Expression of NADPH oxidase components was decreased in renal cortex but induced in aorta. Heme oxygenase-1 (HO-1) was induced in both renal cortex and aorta. In contrast, ANG II suggestively increased AT2 receptor expression in kidney but not in aorta. AT2 receptor blockade enhanced hypertension in ANG II-infused mice, reversed ANG II effects on NOx excretion, but did not affect TBARS. Despite its prohypertensive effect, expression of prooxidative genes in the renal cortex decreased rather than increased after short-term AT2 receptor blockade and renal HO-1 induction after ANG II was normalized. Thus chronic ANG II infusion in mice induces hypertension but not oxidative stress. In contrast to the response in aorta, gene expression of components of NADPH-oxidase was not enhanced in renal cortex. Although ANG II administration induced renal cortical AT2 receptor expression, blockade of that receptor did not unveil the AT2 receptor as intrarenal dampening factor of prooxidative forces.
影响因子：
8.3
作者：
Chabrashvili, T;Tojo, A;Wilcox, CS
通讯作者：
Wilcox, CS
影响因子：
21.1
作者：
Shokei Kim;H. Iwao
通讯作者：
Shokei Kim;H. Iwao